The present invention relates generally to the implantation of devices within a host. More specifically, the present invention relates to the implantation of devices into host tissue that can provide therapeutic materials to the host.
Recent attention has focussed on attempting to surgically implant living cells in a host to treat various diseases, as well as molecular deficiencies. Theoretically, the implanted cells will generate biological products that the host, because of disease, injury, or insult cannot produce for itself. In this regard, for example, the implant assembly can contain pancreatic cells that generate insulin that a diabetic host lacks. Additionally, implanted cells can deliver drugs for therapeutic benefit.
One of the difficulties in implant techniques is providing an implant assembly and methodology that keeps the implanted cells alive long enough to provide the intended therapeutic benefit. In some early attempts to implant pancreatic cells, the cells usually died or became dysfunctional within a few days or weeks after implantation.
For a period of time after implantation, the region of the host tissue next to the implant assembly can be characterized as ischemic. Ischemic means that there is not a sufficient flow of blood in the tissue region closely surrounding the implant assembly. This ischemic condition usually exists during the first two weeks of implantation. In many devices that are implanted, most of the implanted cells, contained within the device, fail to live through this period.
During the ischemic period, a foreign body capsule forms around the implanted cells. The capsule consists of flattened macrophages, foreign body giant cells, and fibroblasts. Originally, conventional hypotheses blamed the foreign body capsule for causing implanted cells to die or become dysfunctional during the ischemic period. However, as noted in U.S. Pat. Nos.: U.S. Pat. 5,314,471 U.S. Pat. 5,344,454 and U.S. patent application Ser. Nos.: 07/606,791 now abandoned; 08/356,787 now pending; and 08/210,068 now pending assigned to the assignee of this patent application, it was discovered that this widely held hypothesis was wrong.
Rather, it was discovered that the cells do not die because of the intervention of the foreign body capsule, but instead, the cells died because conventional implant assemblies and methodologies themselves lack the innate capacity to support the implanted cells ongoing life processes during the critical ischemic period, i.e., the period when the host vascular structures are not nearby. During this time period, the implanted cells perish before the host can grow new vascular structures close enough to the implant assembly to sustain the cells.
In view of this discovery, implant assemblies were created that are so constructed and arranged that they support the growth of vascular structures by the host close to the assembly. Moreover, the assemblies provide high permeability for low molecular weight solutes thereby providing a high metabolic transit value. Using such assemblies, the implanted cells can be isolated within the chamber from the immune response of the host tissue. However, the host grows new vascular structures close to the boundary between the host and the assembly. The vascular structures thereby provide sufficient nutrients to the implanted cells, as well as allow the therapeutic agents generated by the cells to enter the host and be useful therein.
In this regard, the implant assemblies are constructed so that cells are sealed within a cell chamber of the assembly. The implant assembly is then implanted within the host tissue. The assembly is so constructed and arranged that a sufficient metabolic transit value is provided to support the metabolic processes of the implanted cells even in the absence of close vascular structures. This allows the cells to survive during the ischemic period. Within a couple of weeks, formation of new vascular structures around the implant assembly will mark the end of the ischemic period. The structure of the assembly allows nutrients from the host tissue to be received by the cells and allows therapeutic agents from the cells to enter the host tissue.